Chad R. Messick

In vitro synergy testing of levofloxacin, ofloxacin, and ciprofloxacin in combination with aztreonam, ceftazidime, or piperacillin against Pseudomonas aeruginosa

The synergistic potential of levofloxacin, ofloxacin and ciprofloxacin combined with aztreonam, ceftazidime, or piperacillin was compared using 24 strains of Pseudomonas aeruginosa with varying susceptibility profiles. Levofloxacin and ciprofloxacin demonstrated similar in vitro activity, with ofloxacin demonstrating less activity compared to the other agents. Predominantly additive effects were seen with all combinations, with no significant differences detected between the fluoroquinolone agents.

POLYHEXAMETHYLENE BIGUANIDE (PHMB) IN THE TREATMENT OF EXPERIMENTAL FUSARIUM KERATOMYCOSIS

PURPOSE We wanted to determine whether topical polyhexamethylene biguanide (PHMB) 0.02% was effective in the treatment of experimental Fusarium keratomycosis in rabbits. METHODS Fusarium solani keratomycosis was induced in the eyes of 12 New Zealand white rabbits. The rabbits were treated with PHMB 0.02% in one eye and placebo in the other eye for 6 days. The rabbits were evaluated in a masked fashion using a standardized system for clinical progression of the disease. Then the corneas were trephined and growth of F. solani in colony-forming units per milliliter (CFU/ml) determined. RESULTS Clinical evaluation demonstrated no significant mean difference (p > 0.10) in clinical scores between treated and control eyes on day 6 (0.583 +/- 2.503). There was a significant mean CFU difference (p = 0.06) between treated eyes and control eyes (182.5 +/- 314.44). Seven of 12 eyes (58%) in the PHMB group exhibited no growth, whereas two of 12 (17%) eyes reported no growth in the control group. One of 12 eyes (8%) reported > 100 CFU in the PHMB group, whereas seven of 12 eyes (58%) reported > 100 CFU in the control group. CONCLUSIONS PHMB 0.02% was effective in significantly reducing the fungal growth in our rabbit model of Fusarium keratomycosis. The future role of PHMB in the treatment of Fusarium keratitis needs to be further evaluated.

Effects of six-week clarithromycin therapy in corticosteroid-dependent asthma: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND Although corticosteroids such as prednisone are efficacious for the treatment of severe asthma, chronic administration of oral corticosteroid therapy is associated with significant adverse effects. Previous studies have shown that clarithromycin is effective in reducing bronchial hyperresponsiveness and allergen-induced bronchoconstriction. However, the effect of long-term clarithromycin therapy in patients with prednisone-dependent asthma is uncertain. OBJECTIVE This study was conducted to determine the effects of oral clarithromycin on prednisone daily dosage, pulmonary function, quality of life (QOL), and asthmatic symptoms in patients with corticosteroid-dependent asthma. METHODS This 14-week, prospective, randomized, double-blind, placebo-controlled pilot study was conducted at Pulmonary Associates (Phoenix, Arizona) and the University of Illinois at Chicago Medical Center (Chicago, Illinois). Patients aged 18 to 75 years with an established diagnosis of asthma and who had been receiving ≥5 mg/d of prednisone for the preceding 6 months were enrolled. After a 4-week data-collection period, patients received clarithromycin 500 mg BID for 6 weeks, followed by a 4-week follow-up period. The effects of clarithromycin therapy on prednisone dosage requirements, pulmonary function (as assessed using spirometry), QOL, and asthmatic symptoms (nocturnal asthma, shortness of breath, chest discomfort, wheezing, and cough) were assessed. RESULTS Fourteen patients (9 men, 5 women; mean [SD] age, 62 [13] years) completed the study and were included in the final analysis. One patient withdrew from the study due to clarithromycin-related nausea. After 6 weeks of clarithromycin therapy, patients were able to tolerate a significant reduction in mean (SD) prednisone dosage from baseline (30% [18%]; P- 0.020). Pulmonary function, QOL, and asthmatic symptoms did not significantly worsen despite reduction in prednisone dose. All patients who completed the study tolerated clarithromycin therapy. CONCLUSIONS In this pilot study of patients with corticosteroid-dependent asthma, 6-week clarithromycin 500 mg BID was clinically effective in allowing a reduction in prednisone dosage, without worsening pulmonary function, QOL, or asthmatic symptoms. In addition, clarithromycin was well tolerated, with only 1 patient discontinuing therapy due to treatment-related nausea.

Pharmacoeconomic Analysis of Ampicillin-Sulbactam versus Cefoxitin in the Treatment of Intraabdominal Infections

We conducted a retrospective pharmacoeconomic analysis of a prospective, multicenter, double‐blind, randomized, controlled trial comparing the β‐lactamase inhibitor combination ampicillin‐sulbactam (96 patients) and the cephalosporin cefoxitin (101) in the treatment of intraabdominal infections. An institutional perspective was adopted for the analysis. The primary outcomes of interest were cure and failure rates, development of new infection, and antibiotic‐related adverse events. Epidemiologic data pertaining to outcomes was retrieved primarily from the trial, although results of other published studies were taken into consideration through extensive sensitivity analyses. Data pertaining to potential resource use and economic impact were retrieved mainly from the University Health Consortium and hospital‐specific sources. When considering only costs associated with drug acquisition through cost‐minimization analysis, a potential savings of

In vitro activity of chloramphenicol alone and in combination with vancomycin, ampicillin, or RP 59500 (quinupristin/dalfopristin) against vancomycin-resistant enterococci

37.24/patient may be realized with ampicillin‐sulbactam relative to cefoxitin based on an average 7‐day regimen. Outcome data collected for the entire hospitalization during the trial revealed an approximately 9% greater frequency of failure with cefoxitin relative to ampicillin‐sulbactam. When considering all outcomes of interest in the initial base‐case analysis, a potential cost savings of approximately

In vitro bactericidal activity of piperacillin, gentamicin, and metronidazole in a mixed model containing Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis

890/patient may be realized with ampicillin‐sulbactam relative to cefoxitin. In assessing the impact of the significant variability in probability and cost estimates, Monte Carlo analysis revealed a savings of

Postantibiotic Effects and Bactericidal Activities of Clarithromycin–14-Hydroxy-Clarithromycin, versus Those of Amoxicillin-Clavulanate, against Anaerobes

425/patient for ampicillin‐sulbactam over cefoxitin (95% CI

Therapeutic modalities for mechanical cleansing of the colon.

618–1516). Given the model assumptions, our analysis suggests a 78% certainty level that savings will be experienced when ampicillin‐sulbactam is chosen over cefoxitin.

In vitro activity of RPR 106972 alone and in combination with vancomycin, ampicillin, and gentamicin against multidrug-resistant enterococci

Using a checkerboard assay, ampicillin, vancomycin, and RP 59500, each in combination with chloramphenicol, were tested for synergy against 23 isolates of vancomycin-resistant enterococci. Additive effects were seen in 62.5% of the isolates when exposed to chloramphenicol plus RP 59500. Additive effects were observed in 20% and 15% of isolates with chloramphenicol plus vancomycin or ampicillin, respectively. No antagonism was noted.

Levofloxacin and Sparfloxacin: New Quinolone Antibiotics

An anaerobic, mixed model assay was used to study the bactericidal activities of piperacillin, gentamicin, and metronidazole, alone and in double- and triple-antibiotic combinations against a polymicrobial suspension of E. coli, E. faecalis, and B. fragilis. Only slight differences were noted with the agents when tested against single (10(5) cfu/mL inoculum) versus polymicrobic suspensions (10(6) cfu/mL final inoculum) of susceptible and resistant organisms. Contrary to previous reports in the literature, metronidazole was not active against E. coli in an anaerobic environment (even in the presence of B. fragilis) nor was the activity of metronidazole reduced against B. fragilis in the presence of E. faecalis. Gentamicin demonstrated excellent activity against E. coli when tested in a Bactron anaerobic chamber (5% hydrogen, 5% CO(2,) 90% nitrogen). The pH of the media was only reduced to 6.3-6.7, considerably higher than the pH range of 5-6 needed to significantly reduce the activity of aminoglycosides.